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题名: A comparative study on the interactions of human copper chaperone Cox17 with anticancer organoruthenium(II) complexes and cisplatin by mass spectrometry
作者: Li, Lijie1, 2; Guo, Wei1; Wu, Kui1; Wu, Xuelei3; Zhao, Linhong3; Zhao, Yao1; Luo, Qun1; Wang, Yuanyuan1, 4; Liu, Yangzhong3; Zhang, Qingwu2; Wang, Fuyi1, 4
关键词: Organoruthenium complexes ; Cisplatin ; Cox17 ; Anticancer agents ; LC-ESI-MS
刊名: JOURNAL OF INORGANIC BIOCHEMISTRY
发表日期: 2016-08-01
卷: 161, 页:99-106
收录类别: SCI
英文摘要: Herein we report investigation of the interactions between anticancer organoruthenium complexes, [(eta(6)-arene)Ru(en)(CI)]PF6 (en = ethylenediamine, arene = p-cymene (1) or biphenyl (2)), and the human copper chaperone protein Cox17 by mass spectrometry with cisplatin as a reference. The electrospray ionization mass spectrometry (ESI-MS) results indicate much weaker binding of the ruthenium complexes than that of cisplatin to apo-Cox17(2s-s), the functional state of Cox17. Up to tetra-platinated Cox17 adducts were identified while only mono-ruthenated and a little amount of di-ruthenated Cox17 adducts were detected even for the reactions with 10-fold excess of the Ru complexes. However, ESI-MS analysis coupled with liquid chromatography of tryptic digests of metalated proteins identified only three platination sites as Met4, Cys27 and His47 residues, possibly due to the lower abundance or facile dissociation of Pt bindings at other sites. Complexes 1 and 2 were found to bind to the same three residues with Met4 as the major site. Inductively coupled plasma mass spectrometry results revealed that similar to 7 mol Pt binding to 1 mol apo-Cox17(2s-s), molecules, compared to only 0.17 (1) and 0.10 (2) mol Ru to 1 mol apo-Cox17(2s-s). This is in line with the circular dichroism results that much larger unfolding extent of et-helix of apo-Cox17(2s-s), was observed upon cisplatin binding than that upon organoruthenium bindings. These results collectively indicate that Coxl 7 might not participate in the action of these anticancer organoruthenium complexes, and further verify the distinct anticancer mechanism of the organoruthenium(II) complexes from cisplatin. (C) 2016 Elsevier Inc. All rights reserved.
语种: 英语
内容类型: 期刊论文
URI标识: http://ir.iccas.ac.cn/handle/121111/35561
Appears in Collections:活体分析化学实验室_期刊论文

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作者单位: 1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, CAS Key Lab Analyt Chem Living Biosyst, Natl Ctr Mass Spectrometry Beijing,Inst Chem, Beijing 100190, Peoples R China
2.China Univ Min & Technol, Sch Chem & Environm Engn, Beijing 100083, Peoples R China
3.Univ Sci & Technol China, Dept Chem, Hefei 230026, Anhui, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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